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J Infect Dis. 2005 Feb 1;191(3):339-47. Epub 2004 Dec 22.

Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy.

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  • 1British Columbia Centre for Excellence in HIV/AIDS, and Department of Medicine, University of British Columbia, Vancouver, Canada. lab@hivnet.ubc.ca

Abstract

OBJECTIVE:

The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada.

METHODS:

All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations.

RESULTS:

Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001).

CONCLUSION:

High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.

PMID:
15633092
[PubMed - indexed for MEDLINE]
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